【作者】 刘国良；

【导师】 程刚；

【作者基本信息】 沈阳药科大学 ， 药剂学， 2002， 硕士

【摘要】 盐酸氨溴索(Ambroxol HC1)属于新一代祛痰药，能促进支气管分泌物的分泌，并有一定的粘痰稀释作用。它是溴已新的活性代谢物，与第一代和第二代祛痰药相比，它毒性低，祛痰作用强，是最常用的祛痰药之一。为了减少其服药次数，长时间维持有效血药浓度，降低毒副作用，本文采用Compritol 888 ATO作为基本骨架材料，结合其他辅料，制备了日服一次的盐酸氨溴索缓释片。并分别采用体内、体外方法对其进行了科学评价。 建立了紫外分光光度法用于盐酸氨溴索基本理化性质、片剂的释放度和含量的测定；建立了高效液相色谱法，用于检测体内血药浓度，提取回收率为77.5％。以上方法准确可靠，方便快捷，很好地满足了本研究中的各项分析要求。 在处方前研究中，测定了盐酸氨溴索在不同介质中的溶解度，不同pH值下的油／水分配系数，在此基础上，考察了影响盐酸氨溴索缓释片释放的各个因素。主要影响因素是Compritol 888 ATO和乳糖的量。采用中心复合设计试验优化处方，筛选出高、中、低三个不同释放度的处方。 盐酸氨溴索缓释片的初步稳定性试验表明，其对光、热、湿和空气等均较稳定，含量、释放度均无明显变化。加速试验结果预测其有效期可达二年。以扩散的机制释药。 家犬药动学研究表明，用中心复合设计所筛选的盐酸氨溴索缓释片处方，制备日服一次的盐酸氨溴索缓释片在测定时间范围内血药浓度曲线与市售缓释胶囊的相比较为平稳，可维持体内血药浓度达24小时左右；相对生物利用度在80％～125％。统计分析结果显示与参比制剂生物等效；自制缓释片体外释放与体内吸收具有良好的相关性。根据体内外沈阳药科大学硕士学位论文 摘要实验结果得出最优的处方。更多还原

【Abstract】 Ambroxol HCl(AM) is an expectorant drug, promoting bronchial secretion and having mucolytic properties. Ambroxol HCI is a metabolite of bromhexine. Compared with the first and second generation expectorant drugs, it has much more powerful expectorant function and lower toxicity, and is one of most clinically-used expectorant drugs. To reduce the side effects and maintain relatively constant plasma concentration, a sustained release tablet of once daily administration was designed and prepared by using Compritol 888 ATO as basic matrix material.According to the literature, UV spectrophotometer was developed for in vitro assay during the studies of physicochemical properties, content and release. HPLC was applied in the determination of AM in plasma concentration of dogs. The extraction recovery of Ambroxol HCI was 77.5%.In the preformulation researches, the physicochemical properties of Ambroxol HCI were investigated, which benefit pharmaceutical design. Based on the studies of pharmaceutical preformulation, single-factor tests were carried out to screen the influence of formulation and manufacture process on the release of Ambroxol HCI, and three optimal formulations was obtained by Central Composite Design. Ambroxol HCI was released mainly through diffusion during the erosion of matrix tablet. Stability studies of preparation demonstrated that light, temperature, humidity and air had little effect on Ambroxol HCI sustained release tablet (SRT).The studies of pharmacokinetics of ambroxol HCI SRT in dogs verified that the desired purpose of sustained release of ambroxol HCI was achieved, which proved this formulation successful. The plasma concentration maintained for about 24h.Its relative bioavailability was between 80.0% and 125.0%, The result of statistic analysis showes that Ambroxol HCI SRT is bioequivalent with reference preparation. The release of SRT in vitro iscorrelative with the absorption fraction in vivo.更多还原